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存在中和抗体时,子代腺病毒的感染力。

The infectivity of progeny adenovirus in the presence of neutralizing antibody.

机构信息

Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University, Tokyo, Japan.

Division of Cell-Based Therapeutic Products, National Institute of Health Sciences, Kanagawa, Japan.

出版信息

J Gen Virol. 2021 Apr;102(4). doi: 10.1099/jgv.0.001590.

DOI:10.1099/jgv.0.001590
PMID:33843575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8290266/
Abstract

Human adenoviruses (Ads), common pathogens that cause upper respiratory and gastrointestinal infections, are blocked by neutralizing antibodies (nAbs). However, Ads are not fully eliminated even in hosts with nAbs. In this study, we assessed the infectivity of progeny Ad serotype 5 (Ad5) in the presence of nAb. The infectivity of Ad5 was evaluated according to the expression of the Ad genome and reporter gene. Infection by wild-type Ad5 and Ad5 vector continued to increase until 3 days after infection even in the presence of nAb. We established an assay for determining the infection levels of progeny Ad5 using a sorting system with magnetic beads and observed little difference in progeny Ad5 counts in the presence and absence of nAb 1 day after infection. Moreover, progeny Ad5 in the presence of nAb more effectively infected coxsackievirus and adenovirus receptor (CAR)-positive cells than CAR-negative cells. We investigated the function of fiber proteins, which are the binding partners of CAR, during secondary infection, observing that fibre proteins spread from infected cells to adjacent cells in a CAR-dependent manner. In conclusion, this study revealed that progeny Ad5 could infect cells even in the presence of nAb, differing from the common features of the Ad5 infection cycle. Our findings may be useful for developing new therapeutic agents against Ad infection.

摘要

人腺病毒(Ads)是引起上呼吸道和胃肠道感染的常见病原体,可被中和抗体(nAbs)阻断。然而,即使在具有 nAbs 的宿主中,Ads 也不能被完全清除。在本研究中,我们评估了 nAb 存在时亲代 Ad 血清型 5(Ad5)的感染性。根据 Ad 基因组和报告基因的表达评估 Ad5 的感染性。即使存在 nAb,野生型 Ad5 和 Ad5 载体的感染仍持续增加,直到感染后 3 天。我们建立了一种使用磁珠分选系统来确定亲代 Ad5 感染水平的测定方法,并在感染后 1 天观察到 nAb 存在和不存在时亲代 Ad5 计数几乎没有差异。此外,在 nAb 存在的情况下,亲代 Ad5 能够更有效地感染柯萨奇病毒和腺病毒受体(CAR)阳性细胞,而不是 CAR 阴性细胞。我们研究了纤维蛋白在二次感染期间的功能,纤维蛋白是 CAR 的结合伴侣,观察到纤维蛋白以 CAR 依赖的方式从感染细胞传播到相邻细胞。总之,本研究表明,亲代 Ad5 即使在存在 nAb 的情况下也能感染细胞,这与 Ad5 感染周期的常见特征不同。我们的研究结果可能有助于开发针对 Ad 感染的新治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/55c9787adb33/jgv-102-1590-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/a2e312692a7a/jgv-102-1590-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/4b8e96a1294e/jgv-102-1590-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/1a071d3dd679/jgv-102-1590-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/55c9787adb33/jgv-102-1590-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/a2e312692a7a/jgv-102-1590-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/4b8e96a1294e/jgv-102-1590-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/1a071d3dd679/jgv-102-1590-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/8290266/55c9787adb33/jgv-102-1590-g004.jpg

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